The 1.7 kilometre-long train with 55 carriages derailed near Inverleigh along the Hamilton Highway outside Geelong about 5.30am on Monday.
Sixteen of the carriages derailed, sending dozens of shipping containers tumbling.
No one was injured.
"We know there was heavy rainfall and some flash flooding in that area but at this stage it's too early to know what the cause was of the train derailment," Victoria State Emergency Service chief officer Tim Wiebusch told reporters on Monday.
"We are lucky we weren't dealing with a passenger train in this instance and that the crew on board that freight train were also unscathed."
The Australian Rail Track Corporation said no dangerous goods containers were impacted.
The service derailed with containers displaced on both sides of the track and some within an adjoining paddock.
The corporation said the Melbourne-Adelaide rail corridor has been closed and affected customers notified.
The Office of the National Rail Safety Regulator has been notified and the Australian Transport Safety Bureau has taken control of the site.
The bureau's chief investigator for transport safety will conduct the inquiry.
"Investigators will survey the site and collect any relevant components for further examination and analysis," bureau chief commissioner Angus Mitchell said.
"They will also obtain and review any recorded data, weather information, witness reports, and relevant train and track operator records."
Mr Wiebusch said it could take more than a week for the wreck to be removed, as authorities work out how to get heavy machinery to the site.
Victorian Transport Association chief executive Peter Anderson said flooding had been causing significant road and rail freight challenges in the state and called on the state and federal governments to do more to repair the network.
He said with the rail link between Melbourne and Adelaide closed, road freight was expected to increase.
"Freight will always find a way to get to customers and consumers, particularly during our peak season leading into Christmas," Mr Anderson said.
"With the expected increase in heavy vehicle traffic we ask all motorists to take additional care on the roads to prevent accidents and keep everyone as safe as possible."
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